IVF-ICSI

The journey to parenthood may be more challenging for some than others. Fortunately, advancements in technology have made it possible to overcome a variety of fertility issues with the help of Assisted Reproduction Technology (ART), such as in-vitro fertilisation (IVF). These are effective medical techniques that provide safe pathways to achieving a successful pregnancy.

What is assisted reproductive technology?

Assisted reproductive technology (ART) refers to a range of treatments that utilise specialised medical technology to manipulate eggs, sperm or embryos to help couples achieve a successful pregnancy [1]. Infertility is defined by the absence of pregnancy after unprotected and regular sexual intercourse for 12 months. 

ART procedures are generally recommended when less invasive methods are unsuccessful and have helped numerous couples with conception.

Types of assisted reproduction technology

In-vitro fertilisation (IVF)

In vitro fertilisation (IVF) is the most common ART technique performed to achieve pregnancy. The procedure involves handling and fertilising the eggs outside the body, followed by implantation of the resulting embryo into the uterus. Generally, IVF involves the following procedures [1]:

• Ovarian stimulation – The ovaries are stimulated using various agents such as selective oestrogen receptor modulators (e.g. clomiphene citrate, tamoxifen), gonadotropin releasing hormones (luteinising hormone, follicle-stimulating hormones). Typically, a transvaginal ultrasound is used to track the growth of the ovarian follicles; once the follicles are mature enough, human chorionic gonadotropin is administered to trigger ovulation.
  
• Egg retrieval – The eggs released during ovulation are retrieved via a transvaginal needle. The needle aspirates the follicular fluid which contains the egg. The procedure can be performed under general or local anaesthesia to minimise discomfort. Typically, up to 15 eggs are retrieved in one IVF cycle.
  
• Sperm retrieval – Sperm retrieval can be conducted via ejaculation or surgical retrieval in cases such as vas deferens obstruction. The sperms are isolated from the semen before fertilisation.
  
• Fertilisation – During fertilisation, the egg and sperms are mixed in a culture medium and kept in an incubator to allow for fertilisation to take place. Some patients may opt for intracytoplasmic sperm injection (ICSI) to improve fertilisation rates.
  
• Embryo transfer – The embryos are allowed to grow in the culture medium for 3 days (cleavage stage) to 5 days (blastocyst stage) before transferring them into the uterus via a long, thin tube inserted from the vagina. Once transferred, the embryos will implant on the uterine lining and develop further [2]. 

Intrauterine insemination (IUI)

Intrauterine insemination (IUI) involves inserting the sperm directly into the uterus via a long narrow tube to encourage fertilisation. IUI is minimally invasive and inexpensive compared to other forms of ART. Often, medication is given to induce ovulation in combination with IUI to increase the chances of achieving pregnancy. 

Intracytoplasmic sperm injection (ICSI)

ICSI involves injecting a single sperm into the cytoplasm of the egg. ICSI can be performed with IVF in cases where the sperm are unable to fertilise the egg on their own. Typically, ICSI is indicated when male factor infertility is involved, such as low sperm count, and poor sperm function [1, 2]. An ICSI procedure is similar to IVF, with extra procedures involved during fertilisation:

• Sperm selection – An embryologist will carefully select the sperm to be used in the fertilisation procedure from the acquired sperms.
  
• Egg preparation – To prepare for ICSI, the egg is held with a special pipette to stabilise it.
  
• Injection – The selected sperm is injected into the cytoplasm of the egg using a sharp, delicate needle. Once injected, the needle is removed.
  
• Monitoring – The egg is monitored for evidence of a successful fertilisation for the next 24 hours. Multiple eggs can be collected and fertilised in one cycle, the resulting embryos can be transferred into the uterus or cryopreserved for future implantation.

Fertility preservation

Fertility preservation refers to procedures that save the available eggs, embryos, sperms, or other reproductive tissues for future fertility. Fertility preservation procedures can benefit people who:

• Are about to get cancer treatment that may harm their reproductive ability
• Have been exposed to harmful chemicals that may harm their reproductive ability
• Have uterine fibroids or endometriosis
• Are about to receive treatment for autoimmune diseases
• Would like to delay having children

Common forms of fertility preservation include:

Fertility preservation	Description
Egg or sperm cryopreservation	Unfertilised eggs or oocytes and sperms are obtained and cryopreserved for future use.
Embryo cryopreservation	Embryos from IVF or ICSI procedures can be cryopreserved for future use, such as in cases of unsuccessful IVF procedures or for future pregnancies.
Ovarian tissue cryopreservation	Ovarian tissue cryopreservation involves taking the ovarian cortex, the portion that produces eggs, and freezing them. The tissues can be transplanted in the future for pregnancy purposes.
Ovarian transposition	In ovarian transposition, the ovaries (and sometimes fallopian tubes) are relocated to a different part of the patient’s body, such as the abdomen, to prevent radiation exposure to the ovaries. This can be recommended for patients undergoing radiation therapy.
Gonadal shielding	Gonadal shielding involves placing a lead shield to protect the ovaries or testes from radiation exposure, thereby minimising the harm done on the reproductive organs.

When is assisted reproductive technology recommended?

ART treatment indications and recommendations can vary among patients and conditions.

IUI recommendations

IUI can be performed in the following cases [3]:

• Donor sperm – IUI can be performed when fertilisation or conception involves the use of a donor sperm.
  
• Cervical conditions – Infertility due to cervical defects or abnormalities, such as endometriosis, or cervical scarring can be overcome by IUI procedures.
  
• Moderate male factor infertility – IUI can also be indicated for male factor infertility such as low sperm count or poor sperm motility. Typically, a semen analysis is conducted prior to IUI to determine whether the treatment is suitable.
  
• Erectile dysfunction – Men experiencing erectile dysfunction may not be able to engage in sexual intercourse, hence IUI can be done to achieve pregnancy.
  
• Ejaculatory disorders – Certain ejaculatory disorders that lead to difficulty conceiving can be overcome by IUI, such as retrograde ejaculation, where the semen is ejaculated into the bladder.
  
• Immunological factors – Immunological factors indicated in IUI include semen allergy, whereby certain proteins in the semen can cause an allergic reaction. Most of the proteins of the semen are removed before the sperms are inserted, hence preventing an allergic reaction.
  
• Unexplained factors – In certain cases, unexplained infertility can be treated with IUI.

Patient selection for IUI is also important, as several factors can influence pregnancy rates including age, presence of comorbidities, duration of infertility, and sperm motility [4].

IVF recommendations

IVF are typically recommended for the following cases [5]:

• Tubal diseases – Tubal diseases that lead to the obstruction or damage of the fallopian tubes prevent fertilisation. Pregnancies in patients with tubal diseases are also at greater risk of ectopic pregnancies. IVF can be recommended in patients with tubal diseases to overcome tubal factor infertility.
  
• Moderate to severe male infertility – Moderate to severe male fertility, especially after unsuccessful surgical intervention or IUI treatment, can be recommended for IVF treatment.
  
• Severe uterine conditions – Grade III to IV endometriosis can cause infertility, hence IVF treatment can be recommended.
  
• Immunological factors – Immunological factors in IVF commonly involve antisperm antibodies that can immobilise sperm and prevent fertilisation [3].
  
• Unexplained fertility – Unexplained or idiopathic infertility can be recommended for IVF especially if previous IUI treatments were unsuccessful.
  
• Genetic diseases – In some cases, patients opt for preimplantation genetic testing (PGT) to screen for possible inherited diseases before the embryos are transferred into the uterus. These patients are not necessarily infertile.

ICSI recommendations

Generally, ICSI are typically recommended in cases of [6]:

• Severe male factor fertility – ICSI is often indicated for severe male factor infertility, which can include low sperm count, immotile sperms, or abnormal sperm morphology (e.g. globozoospermia).
  
• Immunological factors – Similar to IVF, high amounts of antisperm antibodies can be overcome with ICSI with IVF.
  
• Failed conventional IVF – Typically, ICSI is recommended if at least two rounds of conventional IVF were unsuccessful or had poor fertilisation.
  
• Genetic diseases – ICSI is also often recommended to patients who choose to undergo PGT for inherited diseases.
  
• Using frozen-thawed sperms – Cryopreserved sperms may have lower survivability, hence ICSI can increase fertilisation rates if frozen-thawed sperms are used.

What do I need to know before going for IVF or assisted reproductive technology?

Several factors that may influence the success of live births via ART include [7]:

• Age – Studies have shown that maternal age influences the success rate of live births. The highest chance of successful live births were observed in women aged 25 to 30, where the success rates drop from age 35 onwards.
  
• Cause of infertility – Couples experiencing multiple factors of infertility (e.g. tubal factor, endometriosis, male factor) may experience a higher chance of not having a successful pregnancy or live birth.
  
• Duration of infertility – The duration of infertility can also affect the success rates of achieving a live birth. Typically, couples experiencing longer durations of infertility (6 - 7 years) have a lower success rate than those with shorter durations of infertility (1 - 2 years).
  
• Embryo health – Typically, PGT can be performed before embryo transfer to increase the chance of a healthy embryo being implanted. The quality of the embryo and the day of transfer (embryo stage) can also influence implantation and subsequently pregnancy and birth success rates.
  
• Previous pregnancies – Couples who have had previous pregnancies are more likely to have successful live births compared to those who have none.
  
• BMI – The woman’s BMI may also affect the success rate of a pregnancy, whereby a decline in fertility was observed with an increase of BMI. Additionally, having a low BMI was also associated with an increase in infertility (< 19.5 kg/m²).

It is important that although these factors may influence the likelihood of a pregnancy, it does not define the outcomes of IVF or ART treatments. It is important to discuss your expectations and clear any doubts with your doctor before undergoing assisted reproduction procedures.

What are the risks of assisted reproductive technology?

Studies have also discussed several risks and complications associated with ART treatments [2, 5]:

• Ovarian hyperstimulation syndrome (OHSS) – OHSS is typically observed with the use of human chorionic gonadotropin during egg retrieval. OHSS is characterised by cystic fluid accumulation in the ovaries which can migrate to other spaces in the body. Symptoms of OHSS include:
  • Abdominal distention and discomfort
  • Ovarian enlargement
  • Nausea and vomiting
  • Ascites, fluid accumulation in the peritoneal cavity
  • Breathing difficulties
    
• Multiple pregnancies – Multiple pregnancies can occur because multiple embryos are transferred during ART treatments to increase the chance of successful pregnancies. Several risks associated with multiple pregnancies include Caesarean deliveries, bleeding, pregnancy-associated hypertension (preeclampsia), and gestational diabetes.
  
• Preterm births – ART treatments were observed to be associated with preterm delivery, which refers to the baby being born before 37 weeks of gestation. Other complications also include low birthweight, small for gestational age, risks of stillbirth, and perinatal mortality. However, other factors may also contribute to these risks including the cause of infertility and other biological factors.
  
• Ectopic pregnancy – Incidences of ectopic pregnancy are about 4 times higher in IVF/ICSI than in spontaneous pregnancies. However, other factors can also contribute to this, including tubal factor infertility, transfer of multiple embryos, and the quality of embryos transferred [8, 9].
  
• Developmental issues – Reports regarding cognitive and developmental disabilities associated with ART have been conflicting. It was speculated that the risks of developmental disabilities such as cerebral palsy, autism, and Beckwith-Wiedemann syndrome can be tied to other complications involved, such as preterm delivery and multiple births. Risk factors associated with infertility such as older paternal age, sperm quality, and maternal infertility, are also thought to influence these risks.
  
• Cardiovascular risk – Long-term studies involving ART-conceived individuals showed a likelihood of premature vascular ageing, which may contribute to increased risk for hypertension or other cardiometabolic disorders. However, other factors may also play into this including genetics and environmental factors. Furthermore, the data on ART-conceived individuals are limited, hence the long-term outcomes of ART will only be known in the future.

Summary

Advancements in technology, such as IVF and other assisted reproductive technologies, have offered new hope to couples who face difficulties conceiving. It also benefits those who wish to preserve their fertility for future family planning. Although there is no “best method”, there is one that best suits you and your individual needs. 

To learn more about IVF,  other assisted reproduction modalities, and your options, schedule a consultation with us today for a detailed analysis and personalised treatment plan.